Model membrane size-dependent amyloidogenesis of Alzheimer's amyloid-β peptides
| Autor: | Yuxi Lin, Misaki Kinoshita, Mayu S. Terakawa, Yuji Goto, Erina Kakimoto, Ayyalusamy Ramamoorthy, Tatsuya Ikenoue, Masatomo So, Young-Ho Lee, Toshihiko Sugiki |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Amyloid Kinetics Nucleation General Physics and Astronomy Calorimetry Microscopy Atomic Force Fibril 03 medical and health sciences chemistry.chemical_compound Alzheimer Disease Humans Physical and Theoretical Chemistry POPC Unilamellar Liposomes Amyloid beta-Peptides Chemistry Circular Dichroism Vesicle technology industry and agriculture Peptide Fragments 030104 developmental biology Membrane Biochemistry Phosphatidylcholines lipids (amino acids peptides and proteins) Thioflavin |
| Zdroj: | Physical Chemistry Chemical Physics. 19:16257-16266 |
| ISSN: | 1463-9084 1463-9076 |
| DOI: | 10.1039/c6cp07774a |
| Popis: | We herein report the mechanism of amyloid formation of amyloid-β (Aβ) peptides on small (SUV) and large unilamellar vesicles (LUVs), which consist of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids. Although Aβ1–42 formed fibrils on SUVs at all POPC concentrations used, the lag time, elongation rate, maximum thioflavin T intensity, and fibrillar morphology were distinct, indicating polymorphic amyloid formation. LUVs, at low POPC concentrations, did not markedly affect fibrillation kinetics; however, increases in POPC concentrations suppressed amyloid formation. No significant differences in the thermal stabilities of Aβ1–42 fibrils formed with and without vesicles were observed, although fibrils formed on SUVs showed some differences with dilution. SUVs markedly promoted Aβ1–40 fibrillation by condensing Aβ1–40, whereas no effects of LUVs on amyloidogenesis were detected. Salts greatly increased Aβ1–40 amyloidogenicity on vesicles. We proposed comprehensive models for vesicle size-dependent Aβ amyloidogenesis. Inhomogeneous packing defects in SUVs may induce distinct nucleation in the polymorphisms of amyloids and decreasing local concentrations of Aβ with higher amounts of LUVs inhibits amyloid formation. We also pointed out that C-terminal hydrophobicity of Aβ is important for amyloidogenesis on membranes. |
| Databáze: | OpenAIRE |
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